Hemiretinal Endodiathermy Axotomy (HEA) In Non-Human Primates: Structural Changes by Spectral Domain Optical Coherence Tomography (sdOCT)

Abstract

Purpose : As reported previously, hemiretinal endodiathermy axotomy (HEA) of the inferior retinal nerve fiber bundle in non-human primates (NHPs) isolates the outer retina, resulting in nearly complete loss of axons in the lower half of the optic nerve without disrupting outer retinal anatomy, opsin regulation, retinal or choroidal blood flow. In the present study we used spectral domain optical coherence tomography (sdOCT) to characterize early post-HEA structural changes, to chart the time course of retinal ganglion cell (RGC) loss, to assess development of microcystoid macular degeneration (MMD) and to elucidate the utility of HEA in NHPs as a model for studying outer retinal injury, MMD and RGC degeneration.

Methods : Contiguous endodiathermy spots were placed along the inferior 180° adjacent to the optic nerve margin in the right eyes of 3 young adult rhesus monkeys (1 female, 2 male). A Heidelberg Spectralis HRA+OCT (Heidelberg Engineering) was used to collect macular volume, retinal nerve fiber layer (RNFL) and high resolution single line scans through the fovea at baseline and weeks 1, 2, 4, 8 and 12 post HEA. Segmentation and generation of inner nuclear layer (INL) and RNFL thickness values were accomplished using the EdgeSelect algorithm (EyeKor, LLC).

Results : At week 1 post HEA, the vertical line scans showed slight thickening of the inferior RNFL. At week 2, mild thinning was noted and by week 4 the RNFL was markedly thinned inferiorly while retaining baseline thickness superiorly. By week 12, the RNFL was largely absent inferiorly. (Fig 1) In all three animals, mild MMD was noted at week 8, only in the inferior (axotomized) portion of the eye. MMD was more pronounced at week 12. (Fig 2) The INL appeared thickened prior to onset of MMD.

Conclusions : Thinning of the RNFL was noted as early as two weeks post HEA. Thickening of the INL appears to precede MMD and may have potential as a biomarker. The time course of RGC loss post HEA seems more rapid and predictable than in NHP experimental glaucoma models. RGC axotomy by HEA is a promising alternative to methods such as laser photocoagulation and incisional optic nerve transection and may be useful for studying RGC apoptosis and the contribution of the outer retina in optic neuropathies.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

NFL and RGC layers were markedly thinned inferiorly by 12 weeks post HEA.

 

INL thickness was increased in eyes with MMD.